Congenital hyperinsulinism(CHI) is a rare but complex heterogeneous disorder caused by unregulated secre-tion of insulin from the β-cells of the pancreas leading to severe hypoglycaemia and neuroglycopaenia. Swift di...Congenital hyperinsulinism(CHI) is a rare but complex heterogeneous disorder caused by unregulated secre-tion of insulin from the β-cells of the pancreas leading to severe hypoglycaemia and neuroglycopaenia. Swift diagnosis and institution of appropriate management is crucial to prevent or minimise adverse neurodevel-opmental outcome in children with CHI. Histologically there are two major subtypes of CHI, diffuse and focal disease and the management approach will significantly differ depending on the type of the lesion. Patients with medically unresponsive diffuse disease require a near total pancreatectomy, which then leads on to the de-velopment of iatrogenic diabetes mellitus and pancre-atic exocrine insufficiency. However patients with focaldisease only require a limited pancreatectomy to re-move only the focal lesion thus providing complete cure to the patient. Hence the preoperative differentiation of the histological subtypes of CHI becomes paramount in the management of CHI. Fluorine-18L-3, 4-hydroxy-phenylalanine positron emission tomography(18F-DOPA-PET) is now the gold standard for pre-operative differentiation of focal from diffuse disease and locali-sation of the focal lesion. The aim of this review article is to give a clinical overview of CHI, then review the role of dopamine in β-cell physiology and finally discuss the role of 18F-DOPA-PET imaging in the management of CHI.展开更多
To prepare chiral monomer with single chiral center and higher stereospecificity, a pair of amino-functionalized chiral 3,4-propylenedioxythiophene(ProDOT) derivatives, chiral(3,4-dihydro-2 H-thieno[3,4-b][1,4]dioxepi...To prepare chiral monomer with single chiral center and higher stereospecificity, a pair of amino-functionalized chiral 3,4-propylenedioxythiophene(ProDOT) derivatives, chiral(3,4-dihydro-2 H-thieno[3,4-b][1,4]dioxepin-3-yl)methyl 2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoate(ProDOT-Boc-Phe), were synthesized. Chiral poly[(3,4-dihydro-2 H-thieno[3,4-b][1,4]dioxepin-3-yl)methyl2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoate](PProDOT-Boc-Phe) modified electrodes were synthesized via potentiostatic polymerization of chiral ProDOT-Boc-Phe. Chiral PProDOT-Boc-Phe films displayed good reversible redox activities. The enantioselective recognition between chiral PProDOT-Boc-Phe modified glassy carbon electrodes and DOPA enantiomers was achieved by different electrochemical technologies, including cyclic voltammetry(CV), square wave voltammetry(SWV), and differential pulse voltammetry(DPV).(D)-PProDOT-Boc-Phe and(L)-PProDOT-Boc-Phe showed higher peak current responses toward L-DOPA and DDOPA, respectively.展开更多
A rapid and sensitive method for analyzing trace b-blockers in complex biological samples,which involved magnetic solid-phase extraction(MSPE)coupled with Fourier transform ion cyclotron resonance mass spectrometry(FT...A rapid and sensitive method for analyzing trace b-blockers in complex biological samples,which involved magnetic solid-phase extraction(MSPE)coupled with Fourier transform ion cyclotron resonance mass spectrometry(FTICR-MS),was developed.Novel nanosilver-functionalized magnetic nanoparticles with an interlayer of poly(3,4-dihydroxyphenylalanine)(polyDOPA@Ag-MNPs)were synthesized and used as MSPE adsorbents to extract trace b-blockers from biological samples.After extraction,the analytes loaded on the polyDOPA@Ag-MNPs were desorbed using an organic solvent and analyzed by FTICR-MS.The method was rapid and sensitive,with a total detection procedure of less than 10 min as well as limits of detection and quantification in the ranges of 3.5-6.8 pg/mL and 11.7-22.8 pg/mL,respectively.The accuracy of the method was also desirable,with recoveries ranging from 80.9%to 91.0%following the detection of analytes in human blood samples.All the experimental results demonstrated that the developed MSPE-FTICR-MS method was suitable for the rapid and sensitive analysis of trace b-blockers in complex biological samples.展开更多
BACKGROUND： Parkinson＇s disease （PD） is a common, age-dependent degenerative neurological disorder impairing motor control function and cognition. A key pathology of PD is a degeneration of the nigrostriatal dopam...BACKGROUND： Parkinson＇s disease （PD） is a common, age-dependent degenerative neurological disorder impairing motor control function and cognition. A key pathology of PD is a degeneration of the nigrostriatal dopamine system, leading to a severe dopamine denervation in the striatum and dynsfunction of the striatal neural circuits. OBJECTIVE： To better understand the pathophysiology of the nigrostriatal dopamine denervation and to discover better treatments, animal PD models are needed. METHODS： The authors＇ original research on the transcription factor Pitx3 null mutant mice and the relevant literature were reviewed. RESULTS： An important feature of an animal PD model is the severe, PD-like nigrostriatal dopamine denervation. This feature is provided in the transcription factor Pitx3 null mutant mice. These mice have a severe and bilateral nigral dopamine neuron loss and dopamine denervation in the dorsal striatum, while the dopamine neuron loss in the ventral tegmental area and dopamine denervation in the ventral striatum are moderate, creating a dorsal-ventral dopamine loss gradient and mimicking the dopamine denervation pattern in PD. Pitx3 null mice show motor function deficits in the balance beam and pole tests and these deficits are reversed by L-3,4-dihydroxyphenylalanine （L-dopa）. These mice also show impaired cognitive functions as indicated by reduced motor learning and avoidance memory. L-dopa, D 1 agonists and, to a lesser extent, D2 agonists, induce normal horizontal movements （walking） and also dyskinesia-like movements consisting of vertical body trunk movements and waving paw movements. CONCLUSIONS： The easy-to-maintain Pitx3 null mice with an autogenic, consistent and gradient dopamine denervation are a convenient and suitable mouse model to study the consequences of dopamine loss in PD and to test dopaminergic replacement therapies for PD.展开更多
文摘Congenital hyperinsulinism(CHI) is a rare but complex heterogeneous disorder caused by unregulated secre-tion of insulin from the β-cells of the pancreas leading to severe hypoglycaemia and neuroglycopaenia. Swift diagnosis and institution of appropriate management is crucial to prevent or minimise adverse neurodevel-opmental outcome in children with CHI. Histologically there are two major subtypes of CHI, diffuse and focal disease and the management approach will significantly differ depending on the type of the lesion. Patients with medically unresponsive diffuse disease require a near total pancreatectomy, which then leads on to the de-velopment of iatrogenic diabetes mellitus and pancre-atic exocrine insufficiency. However patients with focaldisease only require a limited pancreatectomy to re-move only the focal lesion thus providing complete cure to the patient. Hence the preoperative differentiation of the histological subtypes of CHI becomes paramount in the management of CHI. Fluorine-18L-3, 4-hydroxy-phenylalanine positron emission tomography(18F-DOPA-PET) is now the gold standard for pre-operative differentiation of focal from diffuse disease and locali-sation of the focal lesion. The aim of this review article is to give a clinical overview of CHI, then review the role of dopamine in β-cell physiology and finally discuss the role of 18F-DOPA-PET imaging in the management of CHI.
基金the National Natural Science Foundation of China(Nos.51762020 and 51603095)the Natural Science Foundation of Jiangxi Province(Nos.20171ACB20026 and20181BAB206015)+4 种基金the Jiangxi Provincial Department of Education(No.GJJ170662)the Innovation Driven"5511"the Natural Science Foundation of Jiangxi Province(No.20165BCB18016)Students Innovation and Entrepreneurship Training Program(No.20181204066)Projects for Postgraduate Innovation in Jiangxi(No.YC2017-X19)the Jiangxi Provincial Key Laboratory of Drug Design and Evaluation(No.20171BCD40015)for their financial support of this work
文摘To prepare chiral monomer with single chiral center and higher stereospecificity, a pair of amino-functionalized chiral 3,4-propylenedioxythiophene(ProDOT) derivatives, chiral(3,4-dihydro-2 H-thieno[3,4-b][1,4]dioxepin-3-yl)methyl 2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoate(ProDOT-Boc-Phe), were synthesized. Chiral poly[(3,4-dihydro-2 H-thieno[3,4-b][1,4]dioxepin-3-yl)methyl2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoate](PProDOT-Boc-Phe) modified electrodes were synthesized via potentiostatic polymerization of chiral ProDOT-Boc-Phe. Chiral PProDOT-Boc-Phe films displayed good reversible redox activities. The enantioselective recognition between chiral PProDOT-Boc-Phe modified glassy carbon electrodes and DOPA enantiomers was achieved by different electrochemical technologies, including cyclic voltammetry(CV), square wave voltammetry(SWV), and differential pulse voltammetry(DPV).(D)-PProDOT-Boc-Phe and(L)-PProDOT-Boc-Phe showed higher peak current responses toward L-DOPA and DDOPA, respectively.
基金supported by the National Natural Science Foundation of China(Grant Nos.:21976168,22127810,and 22004113)Key Research and Development Program of Guangdong Province(Grant No.:2020B1111350002)+1 种基金Guangdong Basic and Applied Basic Research Foundation(Grant No.:2019A1515110420)GDAS0 Project of Science and Technology Development(Grant No.:2021GDASYL-20210103034).
文摘A rapid and sensitive method for analyzing trace b-blockers in complex biological samples,which involved magnetic solid-phase extraction(MSPE)coupled with Fourier transform ion cyclotron resonance mass spectrometry(FTICR-MS),was developed.Novel nanosilver-functionalized magnetic nanoparticles with an interlayer of poly(3,4-dihydroxyphenylalanine)(polyDOPA@Ag-MNPs)were synthesized and used as MSPE adsorbents to extract trace b-blockers from biological samples.After extraction,the analytes loaded on the polyDOPA@Ag-MNPs were desorbed using an organic solvent and analyzed by FTICR-MS.The method was rapid and sensitive,with a total detection procedure of less than 10 min as well as limits of detection and quantification in the ranges of 3.5-6.8 pg/mL and 11.7-22.8 pg/mL,respectively.The accuracy of the method was also desirable,with recoveries ranging from 80.9%to 91.0%following the detection of analytes in human blood samples.All the experimental results demonstrated that the developed MSPE-FTICR-MS method was suitable for the rapid and sensitive analysis of trace b-blockers in complex biological samples.
文摘BACKGROUND： Parkinson＇s disease （PD） is a common, age-dependent degenerative neurological disorder impairing motor control function and cognition. A key pathology of PD is a degeneration of the nigrostriatal dopamine system, leading to a severe dopamine denervation in the striatum and dynsfunction of the striatal neural circuits. OBJECTIVE： To better understand the pathophysiology of the nigrostriatal dopamine denervation and to discover better treatments, animal PD models are needed. METHODS： The authors＇ original research on the transcription factor Pitx3 null mutant mice and the relevant literature were reviewed. RESULTS： An important feature of an animal PD model is the severe, PD-like nigrostriatal dopamine denervation. This feature is provided in the transcription factor Pitx3 null mutant mice. These mice have a severe and bilateral nigral dopamine neuron loss and dopamine denervation in the dorsal striatum, while the dopamine neuron loss in the ventral tegmental area and dopamine denervation in the ventral striatum are moderate, creating a dorsal-ventral dopamine loss gradient and mimicking the dopamine denervation pattern in PD. Pitx3 null mice show motor function deficits in the balance beam and pole tests and these deficits are reversed by L-3,4-dihydroxyphenylalanine （L-dopa）. These mice also show impaired cognitive functions as indicated by reduced motor learning and avoidance memory. L-dopa, D 1 agonists and, to a lesser extent, D2 agonists, induce normal horizontal movements （walking） and also dyskinesia-like movements consisting of vertical body trunk movements and waving paw movements. CONCLUSIONS： The easy-to-maintain Pitx3 null mice with an autogenic, consistent and gradient dopamine denervation are a convenient and suitable mouse model to study the consequences of dopamine loss in PD and to test dopaminergic replacement therapies for PD.
